Recently considerable research, at Yale and elsewhere, has been directed toward the development of targeted imaging agents for noninvasive visualization of myocardial molecular processes such as angiogenesis and ventricular remodeling. Radiolabeled agents directed at molecular targets result in "hotspot" images, which are distinctly different from the "cold spot" images conventionally acquired in nuclear cardiology. This type of cardiovascular hotspot (molecular targeted) imaging requires high sensitivity and high resolution imaging systems. Present single photon emission computerized tomographic (SPECT) imaging technology with conventional collimation does not provide adequate image sensitivity and/or resolution for visualization of these molecular targets. We propose that SPECT imaging with coded aperture collimation may be an alternative imaging technique for acquiring high sensitivity and high resolution images. This technique is particularly suitable for small animal imaging due to the superior performance of coded aperture within a small field of view. In addition to development of new imaging techniques, development of a framework for quantification of these hotspot images is crucial for evaluation of novel new targeted molecular agents. However, quantification of focal uptake in the myocardium is challenging due to heterogeneity of background activity in cardiac SPECT images and lack of quantitative normal reference. In this proposal, the main focus is to develop new approaches for acquisition of high sensitivity and high resolution cardiac SPECT images and new quantitative methods for hotspot imaging. We will focus initially on small animal imaging, but anticipate that the technology and analysis approaches will be readily modifiable for clinical patient imaging. Our specific aims are: 1) To investigate a new collimation technique to improve count statistics for small animal imaging, 2) To improve image resolution of hotspot images using a blind deconvolution method, and 3) To develop and validate a new SPECT quantification method to quantify absolute hotspot activity and volume in the myocardium. Validations for the methods will be performed using phantom studies and a rat model. Ultimately, we anticipate that the proposed imaging technique and SPECT hotspot quantification method will on the one hand, significantly improve image resolution and on the other provide accurate absolute quantitative measurement for hotspot radiotracer uptake in the myocardium. [unreadable] [unreadable]